Non-hodgkin Lymphoma

Question 1

Non-Hodgkin lymphomas are the … most common type of cancer in the UK.

Answer 1

Non-Hodgkin lymphomas are the sixth most common type of cancer in the UK.

Question 2

Lymphoma is a haematological malignancy arising from lymphoid tissue. They are commonly categorised as Hodgkin or Non-Hodgkin lymphoma:

Answer 2

Hodgkin lymphoma (HL): Characterised by the presence of Hodgkin/Reed-Sternberg cells (large, multinucleated cells). Further categorised as classical Hodgkin's lymphoma (nodular sclerosis, mixed cellularity, lymphocyte-rich and lymphocyte-depleted) and nodular lymphocyte-predominant Hodgkin's lymphoma.
Non-Hodgkin lymphoma (NHL): Reed-Sternberg cells are not seen in NHL. There are more than 60 subtypes and they can be B-cell or NK/T-cell in origin. B-cell lymphomas are more common accounting for around 80%, though there is significant geographic variation. NHLs are more common than Hodgkin lymphoma, accounting for around 80-85% of lymphomas.

Question 3

There are around 14,000 cases of .. diagnosed in the UK each year.

Answer 3

There are around 14,000 cases of NHL diagnosed in the UK each year.

Question 4

Epidemiology

There are around 14,000 cases of NHL diagnosed in the UK each year.

Answer 4

In the UK, prevalence increases with age, with most diagnosed after the age of 55 - however it is one of the more common cancers in young people. The 80-84 age-group is most commonly affected.

In 2017, it was the sixth most common cancer in the UK and was responsible for around 4,900 deaths. Overall males are more often affected and there was no significant difference between ethnicities according to figures from Cancer Research UK.

Question 5

The most common symptom of NHL is ….

Answer 5

The most common symptom of NHL is lymphadenopathy.

Question 6

Features common to many NHLs include:

Answer 6

Lymphadenopathy
Fever
Night sweats
Weight loss (unexplained, > 10% in the last 6 months)
Pruritus 
Splenomegaly
Hepatomegaly

Question 7

Together, weight loss, night sweats and fever are called ‘..’ symptoms.

Answer 7

Together, weight loss, night sweats and fever are called ‘B’ symptoms.

Question 8

Some patients will present with primary extra-nodal lymphoma, examples include:

Answer 8

Primary CNS lymphoma: Neurological features such as headache, confusion, seizures and coma may develop.
Primary cutaneous lymphoma: Patients may present with rashes, plaques and ulcers. Examples include mycosis fungoides, a cutaneous T-cell lymphoma.
Primary GI tract lymphoma: Patients may present with abdominal pain, nausea, obstruction and haemorrhage.

Question 9

On occasion patients with NHL may present with, or develop, an oncological emergency.

These include, but are not limited to:

Answer 9

Superior vena cava obstruction (SVCO)
Cord compression
Hypercalcaemia
Tumour lysis syndrome
Neutropenic sepsis

Question 10

Imaging in suspected NHL

Answer 10

Chest x-ray
CT neck, chest, abdomen and pelvis: Allows assessment and identification of enlarged lymph nodes, the liver and spleen and soft tissue masses.
PET CT: Used both in the staging and assessment of treatment response in many lymphomas. Lymphomas are often FDG avid, though some will not be.
MRI brain: Particularly used when leptomeningeal infiltration or mass lesions are suspected.
Testicular USS: Identify suspected testicular lymphoma (a rare type of testicular tumour).
Bone scan

Question 11

Biopsy - Suspected NHL

Answer 11

Excision biopsy of affected lymph nodes or tissue is normally required in patients with suspected NHL.

Needle core biopsy may be considered in those unfit for excisional biopsy. However, if this fails to produce a sufficient sample an excisional biopsy will have to be reconsidered.

Question 12

ADDITIONAL NHL tests

Answer 12

Bone marrow aspirate and biopsy
Lumbar puncture: In patients with suspected CNS disease, cytology and flow cytometry may be required.
Fluorescence in situ hybridisation (FISH): NICE advise using FISH to identify MYC rearrangement in those with high-grade B-cell lymphoma. If found, further testing to identify BCL2 and BCL6 rearrangements and the immunoglobulin partner should be arranged.

Question 13

The … staging system is used to classify NHL.

Answer 13

The Lugano staging system is used to classify NHL.

Question 14

‘B’ symptoms: ‘B’ symptoms refer to fever, night sweats and weight loss (unexplained, >10% in 6 months). ’B’ denotes presence and ‘A’ denotes absence.
Extranodal involvement: In limited stage disease ‘E’ is used to denote extranodal tissue involvement.
Bulky disease: Definition of bulky is nuanced but typically refers to disease > 10cm.

Answer 14

‘B’ symptoms: ‘B’ symptoms refer to fever, night sweats and weight loss (unexplained, >10% in 6 months). ’B’ denotes presence and ‘A’ denotes absence.
Extranodal involvement: In limited stage disease ‘E’ is used to denote extranodal tissue involvement.
Bulky disease: Definition of bulky is nuanced but typically refers to disease > 10cm.

Question 15

R-CHOP

Answer 15

R-CHOP is a commonly used chemotherapy regimen in those with NHL.

Question 16

There are many treatments regimens for NHL. However the one you will be commonly expected to know about at undergraduate level is R-CHOP.

Answer 16

Rituximab: A monoclonal antibody with activity against CD20 - an antigen found on the surface of B-cells. Serious side effects include infusion reactions, hepatitis B reactivation, mucocutaneous reactions and progressive multifocal leucoencephalopathy.
Cyclophosphamide: An alkylating agent, inhibits DNA synthesis through cross linking of DNA. It has carcinogenic tendencies and has been linked to the development of a number of malignancies including transitional cell carcinoma of the bladder. Other serious side effects include bone marrow suppression and infertility.
Doxorubicin: An anthracycline that inhibits topoisomerase II leading to inhibition of DNA and RNA synthesis. Side effects include cardiomyopathy, myelosuppresion and skin reactions.
Vincristine: Inhibits microtubule formation by binding to tubulin. Side effects include peripheral neuropathy and bladder atony.
Prednisolone: Is a glucocorticoid steroid. Its side effects are those of steroids.

Question 17

Diffuse large B cell lymphoma (DLBCL) is the most common form of ..

Answer 17

Diffuse large B cell lymphoma (DLBCL) is the most common form of NHL.

Question 18

… accounts for around 25-30% of all NHL. Within the condition, a number of distinct entities exist and are listed in the WHO classification. It is slightly more common in men than women, and appears to present at a younger age in those of black ethnicity.

Answer 18

DLBCL accounts for around 25-30% of all NHL. Within the condition, a number of distinct entities exist and are listed in the WHO classification. It is slightly more common in men than women, and appears to present at a younger age in those of black ethnicity.

Question 19

Diffuse large B cell lymphoma (DLBCL) is the most common form of NHL.

Answer 19

Patients tend to present with a rapidly enlarging mass, commonly in the neck, abdomen or mediastinum. ‘B’ symptoms are seen in around a third of patients.

Extranodal disease is common and can arise essentially anywhere but is most commonly seen in the GI tract.

Disease in the mediastinum may lead to SVCO whilst bony destruction may result in a presentation with cord compression.

Question 20

Disease in the mediastinum may lead to .. whilst bony destruction may result in a presentation with cord compression.

Answer 20

Disease in the mediastinum may lead to SVCO whilst bony destruction may result in a presentation with cord compression.

Question 21

Treatment of DLBCL

Answer 21

Treatment of DLBCL is enormously complex. Patients will typically be categorised as having limited disease (stage I/II) or advanced disease (stage III/IV). They require assessment for CNS involvement and consideration as to the need for CNS prophylaxis.

Limited stage disease: Is commonly treated with chemoimmunotherapy in the form of R-CHOP. Combined modality therapy (CMT) may be used where chemoimmunotherapy is combined with radiotherapy.
Advanced stage disease: Treatment may involve R-CHOP or other regimens such as (da)-EPOCH-R.

Question 22

… lymphoma is a B-cell NHL, and the second most common form.

Answer 22

Follicular lymphoma is a B-cell NHL, and the second most common form.

Question 23

Follicular lymphoma is the second most common form of NHL. It often presents insidiously, with gradual lymphadenopathy.

The exact pathogenesis is not understood. Around 85% have a translocation between chromosomes 14 and 18, t(14;18), however this is a non-specific change that may be seen in many without lymphoma.

Answer 23

Follicular lymphoma is the second most common form of NHL. It often presents insidiously, with gradual lymphadenopathy.

The exact pathogenesis is not understood. Around 85% have a translocation between chromosomes 14 and 18, t(14;18), however this is a non-specific change that may be seen in many without lymphoma.

Question 24

Answer 24

Follicular lymphoma is the second most common form of NHL. It often presents insidiously, with gradual lymphadenopathy.

The exact pathogenesis is not understood. Around 85% have a translocation between chromosomes 14 and 18, t(14;18), however this is a non-specific change that may be seen in many without lymphoma.

Question 25

Presentation

Follicular lymphoma often presents …

Answer 25

Presentation

Follicular lymphoma often presents in an insidious manner with gradually worsening, painless lymphadenopathy. The degree of lymphadenopathy may ‘wax and wane’ over time. ’B’ symptoms of weight loss, fever and night sweats are sometimes present.

Question 26

Treatment of follicular lymphoma depends on …

Answer 26

Treatment of follicular lymphoma depends on the stage at diagnosis. For disease caught in the earlier stages (Stage I / II) local radiotherapy may be offered. In those with Stage II disease, or higher grade disease, treatment may more mirror that described for advanced stage disease. ’Watch and wait’ can be used in those in whom radiotherapy is unsuitable.

Cure is not common in those with stage II, III and IV disease and relapse is frequently seen. In patients with stage III/IV disease (advanced disease) and some with stage II, treatment depends on whether or not they are symptomatic. Treatment may involve immunotherapy with rituximab in those who are asymptomatic. In patients who are symptomatic chemoimmunotherapy is frequently offered with rituximab combined with chemotherapy regimens (e.g CVP, CHOP)

Question 27

Burkitt’s lymphoma

Answer 27

Burkitt’s is a high-grade, rapidly proliferating, B-cell NHL, that commonly affects children.

Question 28

Burkitt’s is a high-grade, rapidly proliferating, B-cell NHL, that commonly affects children.

Answer 28

In the UK Burkitt’s is relatively uncommon, with around 210 cases each year. It is the most common NHL in children in the UK and it more frequently affects males.

Question 29

In the UK Burkitt’s is relatively uncommon, with around 210 cases each year. It is the most common NHL in children in the UK and it more frequently affects males.

It may be grouped into three types:

Answer 29

Endemic: Strongly associated with Epstein-Barr virus (EBV), and follows the distribution of malaria. It is often seen in equatorial Africa.
Sporadic: Less commonly associated with EBV, often seen in Europe and North America.
Immunodeficiency: Associated with AIDs or in other conditions / medications that lead to immunosuppression.

Question 30

Burkitt’s lymphoma

Answer 30

Endemic Burkitt’s classically presents with a rapidly enlarging tumour in the jaw of a child. It can also present with enlarged lymph nodes in the neck and abdominal masses.

Sporadic Burkitt’s more commonly presents with abdominal symptoms, with the ileoceacal valve often affected. It may present with bowel obstruction.

Fever, weight loss and night sweats may all be present.